We plan to continue to accumulate HLA data in families of well documented ascertainment with the aim of achieving statistical significance in tests that discriminate between different modes of inheritance. Second-degree relatives will continue to be tested both clinically and serologically in order to obtain independent evidence as to population gene frequences for JDM-P and pentrance in different environments. ICA studies will be continued in cooperation with Dr. Abner Notkins of the Institute for Oral Diseases (NIH) in order to establish the relationship between ICA (and, hopefully, beta-cell surface antibody as well) and genetic susceptibility to JDM. Work on the influence of different HLA markers, including beta f, is also progressing and will be probably ready for critical evaluation as we expect to accumulate complete data in over 200 pedigrees. Finally, we plan to begin exploring the mechanism of action of the putative JDM-P gene at the level of beta-cells in vitro, in work supported initially by non-NIH sources.